Transforming Growth Factor β1 Regulates Tissue Inhibitor of Metalloproteinases—1 Expression in Differentiated Human Articular Chondrocytes

Günther, Monika; Haubeck, H.-D.; Leur, Eddy Van de; Bläser, Jörg; Bender, S.; Gütgemann, Ines; Fischer, Dagmar‐Christiane; Tschesche, Harald; Greiling, H.; Heinrich, Peter C.; Graeve, Lutz

doi:10.1002/art.1780370314

Cited by 94 publications

(55 citation statements)

References 53 publications

(26 reference statements)

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“…It is currently believed that TGFP has a profound stimulatory effect on TIMP-1 production (21). These findings were also confirmed in the present study, which showed the same magnitude as that of OSM.…”

Section: Discussionsupporting

confidence: 91%

“…The use of the identical signal-transducing molecule, gp130, which has been reported to be expressed on human chondrocytes (21), suggests that the biologic effects of these cytokines on the metabolism of the connective tissue cells are qualitatively similar. Since IL-6 family cytokines have been reported to stimulate TIMP-1 synthesis in fibroblasts (26), we investigated whether these findings are also confirmed in chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Lotz and Guerne (19) reported that IL-6 induced TIMP-1 synthesis in monolayer cell cultures, while Giinther et a1 (21) demonstrated that IL-6 failed to stimulate TIMP-1 synthesis in both monolayer and agarose cell cultures. These contradictory results may be due to the use of different culture systems.…”

Section: Discussionmentioning

confidence: 99%

“…It is evident that interleukin-1 (IL-1) and tumor necrosis factor a (TNFa) are among the most potent stirnulators of MMP production in human chondrocytes (16)(17)(18). Similarly, regulation of TIMP-I synthesis by cytokines and growth factors such as , IL-I 1 (20), and transforming growth factor P (TGFP) (21) has been observed in human chondrocytes, but the stimulation of TIMP-1 synthesis b y these factors, especially by IL-6, has not been well established.…”

mentioning

confidence: 99%

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Stimulation of TIMP‐1 production by oncostatin m in human articular cartilage

Nemoto

Yamada

Mukaida

et al. 1996

Arthritis & Rheumatism

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Objective. To investigate the effects of the interleukind (IL-6) family cytokines, such as IL-6, IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM), on the production of tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in human articular cartilage.Methods. Effects of IL-6 family cytokines and growth factors on TIMP-1 production were studied in human articular chondrocytes, grown as monolayer and cartilage explant culture. TIMP-1 protein levels in the cultured medium were measured by sandwich enzyme immunoassay. TIMP-1 messenger RNA levels in the cultured chondrocytes were analyzed by Northern blotting. Western blot analysis was performed to evaluate the release of matrix metalloproteinases (MMPs) in the cultured medium. Cell proliferation of chondrocytes was determined by 3H-thymidine uptake.Results. IL-6 family cytokines induced TIMP-1 expression in monolayer and explant culture, and the production of TIMP-1 was most stimulated by OSM. In contrast, OSM did not modulate the release of MMPs and cell proliferation.Conclusion. These results suggest that OSM may be characterized as one of the chondroprotective mediators in cartilage destruction.Osteoarthritis (OA) is one of the most common disorders of the human joints. It is characterized by a gradual loss of the extracellular matrices of articular cartilage, such as proteoglycan (PG) and type I1 collagen (1,2). It is well known that extracellular matrices -~-

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Stimulation of TIMP‐1 production by oncostatin m in human articular cartilage

Nemoto

Yamada

Mukaida

et al. 1996

Arthritis & Rheumatism

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“…We and others (14,15,36) showed that TGF-␤ can increase PTG synthesis in normal and OA chondrocytes in vivo and in vitro. Furthermore, local administration of TGF-␤ can suppress IL-1-induced matrix degradation (17,37), probably via down-regulating MMPs (38, 39) and/or increasing the level of TIMPs (38,40). TGF-␤ also inhibits terminal differentiation of chondrocytes (hypertrophy), which has been shown to occur during OA.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Scharstuhl

Glansbeek

Beuningen

et al. 2002

The Journal of Immunology

218

157

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Osteoarthritis has as main characteristics the degradation of articular cartilage and the formation of new bone at the joint edges, so-called osteophytes. In this study enhanced expression of TGF-β1 and -β3 was detected in developing osteophytes and articular cartilage during murine experimental osteoarthritis. To determine the role of endogenous TGF-β on osteophyte formation and articular cartilage, TGF-β activity was blocked via a scavenging soluble TGF-β-RII. Our results clearly show that inhibition of endogenous TGF-β nearly completely prevented osteophyte formation. In contrast, treatment with recombinant soluble TGF-β-RII markedly enhanced articular cartilage proteoglycan loss and reduced the thickness of articular cartilage. In conclusion, we show for the first time that endogenous TGF-β is a crucial factor in the process of osteophyte formation and has an important function in protection against cartilage loss.

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Modulation of the catabolic effects of interleukin-1β on human articular chondrocytes by transforming growth factor-β

et al. 1996

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The effects of IL-1 beta and TGF-beta on the biosynthesis of extracellular matrix structural components relative to the metalloproteinases and their inhibitor TIMP1 in human articular chondrocytes were investigated. It has been proposed that TGF-beta, acting as a positive regulator of matrix accretion, can counteract the increased loss of cartilage matrix induced by IL-1 beta. To allow a comparison of their effects on mRNA levels for these different components, quantitation by competitive RT/PCR was employed. This method was found to give reproducible estimates of mRNA levels and the observed effects of IL-1 beta and TGF-beta on individual components of this system agree with qualitative data obtained by northern blotting. IL-1 beta had a more pronounced effect on aggrecan mRNA levels than on those for type II collagen. Similar quantitative differences were observed between collagenase and stromelysin mRNA levels. TGF-beta generally counteracted the effects of IL-1 beta, and new steady state levels were attained within 24 h. However, the reversal of IL-1 beta induced suppression of matrix protein mRNA levels appeared more effective than its suppression of the increase in stromelysin and collagenase mRNA levels. Similarly TGF-beta did not reduce the extent of IL-1 beta induced secretion of stromelysin at the protein level. TIMP1 mRNA levels were only slightly reduced by IL-1 beta; however this cytokine effectively suppressed its induction by TGF-beta. The higher concentrations of TGF-beta and longer exposure times required to overcome the suppressive effects of IL-1 beta suggest that the interaction between IL-1 beta and TGF-beta in the regulation of TIMP1 expression follows a different mechanism to that operating for the metalloproteinases and matrix proteins. Thus the overall potential of TGF-beta to inhibit proteolysis is attenuated by its much slower effect on TIMP1 mRNA levels.

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Transforming Growth Factor β1 Regulates Tissue Inhibitor of Metalloproteinases—1 Expression in Differentiated Human Articular Chondrocytes

Cited by 94 publications

References 53 publications

Stimulation of TIMP‐1 production by oncostatin m in human articular cartilage

Stimulation of TIMP‐1 production by oncostatin m in human articular cartilage

Inhibition of Endogenous TGF-β During Experimental Osteoarthritis Prevents Osteophyte Formation and Impairs Cartilage Repair

Modulation of the catabolic effects of interleukin-1β on human articular chondrocytes by transforming growth factor-β

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